ABSTRACT Peripheral arterial disease may lead to critical limb ischemia and results in amputation of the limb in severe manifestations. The prevalence rate of peripheral arterial disease increases from 0.9% in those younger than 50 years to 14.5% in those 70 years or older. In the United States, over 8 million individuals have lower extremity PAD, with combined annual costs exceeding $21 billion. Surgical bypass of the diseased peripheral arterial segment is one of the main treatments for the patients with life-limiting claudication or critical limb ischemia. Autogenous vein graft is the most commonly used conduit in the bypass surgery. Unfortunately, there are a limited number of bypasses that can be made from autogenous vein grafts. Current alternative approaches include synthetic material, acellular scaffolds, and tissue-engineered grafts, but all have failed to produce a functional small diameter graft. Thus, there is a critical need for readily available grafts for bypass surgery. In this proposal, we will evaluate the pulmonary visceral pleura (PVP) as a novel biological scaffold for bypass surgery in peripheral arterial disease. Our group has preliminary data showing small diameter (~0.70 mm) glutaraldehyde-fixed PVP grafts remain patent at 9 months in a rat model where the graft fully and functionally arterializes and with no indications of calcification or aneurysm. In this proposal, we aim to expand upon our preliminary findings and evaluate the safety and efficacy of PVP as small diameter (~ 3 mm) grafts for peripheral artery surgery in a swine model. This proposal addresses a clinically very significant problem and successful completion will provide surgeons with numerous conduit size options, to minimize SV harvesting, and reduce procedure time and healthcare costs.